The proposed research is aimed at investigating the relationship between hypertension and various aspects of the intraerytherocytic sodium metabolism (sodium-lithium countertransport, sodium-potassium cotransport, intracellular sodium and potassium content). A multidisciplinary approach will be used focusing on both epidemiological and controlled nutritional experimental investigations. The epidemiological investigation will be carried out using both cross- sectional and longitudinal data from an ongoing large population-based study. The data from this investigation will be used to: a)study the distribution and the determinants of these intracellular ion metabolism parameters in the population; b) investigate the association between these parameters and hypertension both in the overall population as well as in sex-age subgroups; c) analyze the mode of inheritance of these aspects of the intracellular ion metabolism; d) address the critical issue of whether or not alteration in these ion transport parameters are associated with the future risk of developing hypertension. The nutritional experimental investigation will attempt to clarify the interrelationships among specific nutrition interventions (sodium restrictions, calcium supplementation), the intracellular ion metabolism parameters, and blood pressure, in both normotensives and hypertensives of the black and white race. In particular, two major questions will be posed: a) whether or not these intracellular sodium transport parameter are indicative of the blood response to the specific nutrition intervention, and b) whether or not the changes in blood pressure due to the nutritional intervention are related to changes in the intracellular ion transport parameters. The importance of the proposed study is two- fold: The epidemiological investigation proposed is unique because: 1) it is the largest population-based study on intracellular ion transport and hypertension to date, b) it provides information on a large number of families, allowing the study of the mode of inheritance of these intracellular ion transport parameters, c) it is to date the only study that will provide longitudinal data on the importance of these parameters in the risk of developing hypertension. The nutritional investigation may help to identify the basis for individual differences in blood pressure response to sodium or calcium intake and may provide a tool for identifying individuals who may benefit from a specific nutritional approach.